Variant 6-44403977-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001253.4(CDC5L):c.708C>T(p.Asp236Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,612,186 control chromosomes in the GnomAD database, including 20,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2743 hom., cov: 32)

Exomes 𝑓: 0.12 ( 17742 hom. )

Consequence

CDC5L
NM_001253.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

CDC5L (HGNC:1743): (cell division cycle 5 like) The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

CDC5L links:

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

POLR1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 6-44403977-C-T is Benign according to our data. Variant chr6-44403977-C-T is described in ClinVar as [Benign]. Clinvar id is 1228167.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4 linkuse as main transcript	c.708C>T	p.Asp236Asp	synonymous_variant	6/16	ENST00000371477.4	NP_001244.1	Q99459
CDC5L	XM_047419605.1 linkuse as main transcript	c.273C>T	p.Asp91Asp	synonymous_variant	2/12		XP_047275561.1
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-37913C>T		intron_variant			NP_001305805.1	O15160-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4 linkuse as main transcript	c.708C>T	p.Asp236Asp	synonymous_variant	6/16	1	NM_001253.4	ENSP00000360532.3		Q99459

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23119

AN:

151712

Hom.:

2741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.170

AC:

42594

AN:

250284

Hom.:

6455

AF XY:

0.173

AC XY:

23434

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.623

Gnomad SAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.0821

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.119

AC:

173310

AN:

1460356

Hom.:

17742

Cov.:

AF XY:

0.123

AC XY:

89591

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.0835

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.152

AC:

23141

AN:

151830

Hom.:

2743

Cov.:

AF XY:

0.160

AC XY:

11852

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.611

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0836

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.0992

Hom.:

1281

Bravo

AF:

0.153

Asia WGS

AF:

0.476

AC:

1652

AN:

3478

EpiCase

AF:

0.0817

EpiControl

AF:

0.0790

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.9

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over